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Research article Eρευνητική εργασία Fatigue and somatic anxiety in patients with major depression P.P. Ferentinos, V.P. Kontaxakis, B.J. Havaki-Kontaxaki, D.G. Dikeos, G.N. Papadimitriou 1st Department of Psychiatry, University of Athens, Eginition Hospital, Athens, Greece

Psychiatriki 2009, 20:312–318

T

he objective this study aimed to investigate the independent contribution of somatic anxiety to the severity of depression-related fatigue. Seventy-six patients (85.5% female), aged 23–65 years (mean 48.7±10.6), diagnosed with major depressive disorder and currently in a major depressive episode (ΜΙΝΙ 5.0.0.) with a 17-item Hamilton Depression Rating Scale (HDRS) score ≥17, were studied. Forty-nine patients (64.5%) were concurrently suffering from anxiety disorder(s). Patients with physical diseases or other fatigue-related conditions were excluded. Reported fatigue was measured with the 14-item Fatigue Questionnaire (FQ). Based on HDRS item 11 (somatic anxiety) scores, patients were divided into those with somatic anxiety (HDRS-11≥2) and those without (HDRS-11≤1). Pearson’s (r) and Spearman’s (rho) correlations between FQ score, age, gender, inpatient status, HDRS score and somatic anxiety status were calculated. A multiple regression analysis was then performed, with FQ as the dependent variable. Fifty-seven patients (75%) were rated as suffering from somatic anxiety (HDRS-11≥2). Patients with somatic anxiety had significantly higher HDRS and FQ scores. The FQ score significantly correlated with the HDRS score (r=0.36, p=0.001) and somatic anxiety status (rho=0.35, p=0.002). The FQ score was independently predicted by HDRS score and somatic anxiety status, with standardised beta coefficients of 0.259 (p=0.028) and 0.255 (p=0.031), respectively. R2 was 0.185. Both the severity of depression and the presence of somatic anxiety independently correlate with the severity of reported fatigue in patients with major depression. This finding has potential implications for the management of depression-related fatigue. Key words: Major depression, somatic anxiety, fatigue.

PSYCHIATRIKI 20 (4), 2009

FATIGUE AND SOMATIC ANXIETY IN PATIENTS WITH MAJOR DEPRESSION

Introduction Fatigue is a frequent symptom in the general population and one of the principal presenting symptoms in primary care facilities.1,2 Fatigue is also associated with a wide variety of conditions (physical diseases, neurological or psychiatric disorders, chronic fatigue syndrome), in which it is a major determinant of prognosis and functional capacity. 3 Various self-report measures have been introduced to assess the severity and prevalence of fatigue in various settings.4,5 The Fatigue Questionnaire6 is the most widely used multidimensional measure assessing the intensity of reported fatigue-related symptoms. Depressive and anxiety symptoms are prevalent in many fatigue-related conditions and have been found to correlate with the severity of reported fatigue. Studies in the community and in primary care settings have found that the severity of reported fatigue correlates with the severity of both depression and anxiety.7–10 Furthermore, several studies have isolated strong independent correlations between the severity of reported fatigue and the intensity of depressive and anxiety symptoms in patients with fatigue-related diseases or conditions, such as multiple sclerosis,11–13 Parkinson’s disease,14 cancer,15,16 HIV infection,17,18 fibromyalgia,19,20 systemic lupus erythematosus,21–23 sleep apnea,24 and chronic fatigue syndrome.25–27 Fatigue is a core symptom of major depression as well as a prodromal and a residual symptom of depressive disorders.28,29 It is prevalent in 73–97% of depressed patients and has a detrimental impact on their level of functioning and quality of life.30,31 However, fatigue in major depression is understudied compared to other fatigue-related conditions. A few studies have recently attempted to isolate predictors of depression-related fatigue; female gender, sleep disturbances and the severity of depression are the main ones that have been located.32–35 Depressed patients often suffer from comorbid anxiety disorders or subthreshold anxiety symptoms.36,37 However, the independent contribution of somatic anxiety symptoms (i.e. effects of autonomic overactivity) to the severity of depression-related fatigue has not been investigated and this was the objective of this study. The isolation of potential additional predictors of depression-related fatigue might allow

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clinicians to manage this debilitating symptom in a more specific and efficient way. Material and method Subjects

Subjects included in the study were consecutive patients of both sexes, aged 18–65 years, who were either hospitalized in one of the wards of the Psychiatric Clinic, or treated at the outpatient service of Eginition Hospital from March 2005 to March 2007. All patients had a diagnosis of Major Depressive Disorder (MDD) and were currently in a Major Depressive Episode (MDE), as assessed by the short structured DSM-IV-based interview ΜΙΝΙ version 5.0.0.38 Moreover, all patients had a 17-item Hamilton Depression Rating Scale (HDRS)39 score ≥17.40 Exclusion criteria were: (1) other diagnoses interfering with patients’ cooperation in the study (catatonic or psychotic features in the present episode, organic mental disorders, mental retardation), (2) other DSMIV axis I mental disorders except anxiety disorders (alcohol or other substance abuse during the last 6 months, eating disorder during the last 6 months, sleep disorders) potentially associated with clinically significant fatigue, (3) severe physical diseases or other fatigue-related conditions (severe obesity with BMI>45, pregnancy, fatigue-associated medications except psychotropics), (4) a recent (i.e. less than 3 weeks ago) change in the drug treatment regimen. All patients had their medical history recorded. A thorough physical examination was carried out and blood was drawn for a biochemical profile, total blood count and basic endocrinological tests within ±2 days from the clinical/psychometric evaluations. Patients were further tested once clinical evaluations and routine laboratory tests provided evidence for physical diseases potentially associated with prominent fatigue. When patients met one or more of the exclusion criteria, they did not enter the analyses. All patients were asked to provide written informed consent before participating in the study. The study protocol was approved by the Research Ethics Committee of Eginition Hospital. Subjects finally included were 76 patients, aged between 23 and 65 years (mean 48.7±10.6 years); 65 were females (85.5%) and 38 (50%) were inpatients. Forty-nine

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patients (64.5%) were concurrently suffering from anxiety disorder(s), as assessed with the ΜΙΝΙ. The majority of patients (N=63, 82.9%) were under antidepressant medication (47.4% on SSRIs and 35.5% on SNRIs).

2) as a cut-off point, patients were divided into those with somatic anxiety (HDRS-11 score ≥2) and those without (HDRS-11 score ≤1).

Measures

Descriptive statistics were used to check the distributions of all variables. Student’s independent samples t-test or Mann-Whitney U test (as appropriate) and Pearson Chi-square test were used for the comparison of continuous and categorical variables, respectively, between patients with somatic anxiety and those without. Pearson’s (r) and Spearman’s (rho) coefficients were employed in bivariate correlations between the FQ score as the dependent variable and the independent variables (age, gender, inpatient status, HDRS score and somatic anxiety status), as well as in intercorrelations between the independent variables to test for collinearity.

The following instruments were used for cross-sectional assessment of the severity of fatigue and depression. Fatigue

The severity of fatigue during the last two weeks prior to assessment was recorded by means of the Fatigue Questionnaire (FQ), a frequently used, established, self-report fatigue questionnaire, comprising 14 items measuring the intensity of fatigue-related symptoms. Each item is rated on a 4-point Likert scale (0 "better than usual", 1 "no more than usual", 2 "worse than usual", 3 "much worse than usual"). The FQ score is the sum of all items’ scores. Greek translation and back translation of the FQ was made according to the guidelines of the World Health Organization.41 The FQ consists of two subscales: a mental and a physical fatigue subscale.6 Depression

The severity of depression was assessed with the 17-item HDRS, which is one of the most widely used observer-rated instruments to assess the severity of depressive symptoms in MDD patients. Ratings are completed by the examiner on the basis of patient interview (depressive symptoms experienced over the past week), information provided by relatives or nurses and observations. Eight items are scored from 0 to 2 and nine items are scored from 0 to 4. A cut-off point of 17 is often used to ensure a degree of depression severity.40 Somatic anxiety

HDRS item 11 measures somatic anxiety and includes physiological concomitants of anxiety, i.e. "butterflies", indigestion, stomach cramps, belching, diarrhoea, palpitations, hyperventilation, paraesthesias, sweating, flushing, tremor, headache, urinary frequency.39. It is rated on a 5-point Likert scale (0=absent, 1=mild, 2=moderate, 3=severe, 4=incapacitating). Using the median HDRS item 11 score (i.e.

Statistical analysis

Then, a stepwise multiple regression analysis was performed, with the FQ score as the dependent variable, so as to isolate independent predictors of the severity of fatigue. Any variable found to correlate with the FQ score at a p2. Fifty-seven patients (75%) were rated as suffering from somatic anxiety (HDRS-11 score ≥2). Patients with somatic anxiety did not significantly differ from those without in age (t=0.19, df=74, P=0.85), gender (x2=0.89, p=0.35) and inpatient status (x2=0.63, p=0.43). However, patients with somatic anxiety had significantly higher scores both on the HDRS (t=3.83, df=74, p